Article
Biochemistry & Molecular Biology
Eva S. Schoenegger, Antony Crisp, Marco Radukic, Jonas Burmester, Thomas Frischmuth, Thomas Carell
Summary: Post-synthetic modification of nucleic acid structures with clickable functionality is a versatile tool that improves the performance and applicability of nucleic acids. This study presents a simple and feasible technology to modify DNA and RNA strands at both ends. This method helps to synthesize highly functionalized oligonucleotides, enhancing their therapeutic and diagnostic applications.
Article
Biochemistry & Molecular Biology
Erwin Doe, Hannah L. L. Hayth, Ross Brumett, Emil F. F. Khisamutdinov
Summary: Nucleic acid-based therapeutics involve conjugating small molecule drugs to nucleic acid oligomers to overcome solubility challenges and the inefficient delivery into cells. Click chemistry has emerged as a popular approach due to its simplicity and high conjugation efficiency. However, the purification of oligonucleotide conjugates is a major drawback. This study introduces a simple and rapid purification method using MWCO centrifugation to separate excess unconjugated molecules and toxic catalysts for nucleic acid nanotechnology applications.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2023)
Article
Chemistry, Physical
Radostina Kalinova, Kirilka Mladenova, Svetla Petrova, Jordan Doumanov, Ivaylo Dimitrov
Summary: This study successfully synthesized two types of polymer-oligonucleotide conjugates and formed SNAs with biodegradable cores. The nano-assemblies showed no cytotoxicity in vitro and exhibited good interactions with membrane lipids, suggesting their potential application in gene therapy.
Article
Polymer Science
Shizuka Tane, Tsuyoshi Michinobu
Summary: 1,8-Carbazole-based conjugated polymers were successfully synthesized via Cu(I)-catalyzed azide-alkyne cycloaddition, displaying selective metal ion recognition and fluorescence chemosensor behavior only in unsubstituted carbazole position. Among the studied metal cations, Sn2+ ions showed the strongest binding affinity to the polymer.
POLYMER INTERNATIONAL
(2021)
Review
Chemistry, Analytical
Zhaohe Huang, Sitong Liu, Xiaojing Pei, Shujing Li, Yifan He, Yigang Tong, Guoqi Liu
Summary: This review discusses the importance and development of CRISPR/Cas system in nucleic acid detection applications. The combination of CRISPR with various signal-readout techniques has wide applications in molecular diagnostics. Fluorescence is a dominant read-out technique, and understanding fluorescence readout types and variables affecting the signals can improve experimental designs.
Article
Chemistry, Multidisciplinary
Obianuju A. Nwokolo, Brant Kidd, Te'Kara Allen, Alexander S. Minasyan, Suchitra Vardelly, Kristopher D. Johnson, Irina V. Nesterova
Summary: In this study, a memory-based sensor was designed based on the unique kinetic properties of nucleic acid quadruplexes to measure heat changes in small open systems. The sensors are biocompatible, operate homogeneously, and measure small heats released over long time periods, and have been successfully applied to water/propanol mixing and ligand/protein binding.
ANGEWANDTE CHEMIE-INTERNATIONAL EDITION
(2021)
Review
Chemistry, Applied
Farid Ahmed, Hai Xiong
Summary: This review summarizes the latest developments in chemosensors based on click generated triazoles for a range of metal cations, anions, and neutral analytes, highlighting the need for continuous research accumulation in this rapidly growing field to meet demand.
Article
Chemistry, Multidisciplinary
Lajos Kovacs
Summary: Nucleic acids are crucial for life processes. The synthesis of analogues and investigation of their properties have provided insights into the essential characteristics of these building blocks. The accidental discovery of a side reaction led to the development of a new peptide sequencing method. The study of guanine derivatives and their properties further advanced the understanding of supramolecular systems composed of purine analogues.
Article
Multidisciplinary Sciences
Tiberiu S. Mihaila, Carina Bate, Lynn M. Ostersehlt, Jasmin K. Pape, Jan Keller-Findeisen, Steffen J. Sahl, Stefan W. Hell
Summary: With the recent advancements in fluorescence nanoscopes, the ability to dissect nanoscopic biological structures is limited by the size of protein labels. Bioorthogonal chemical groups provide a powerful tool for specific detection of biomolecules. In this study, we introduced an engineered aminoacyl-tRNA synthetase/tRNA pair to allow for the site-specific introduction of amino acids with clickable side chains into proteins. This enhanced genetic code expansion machinery was then used to label beta-actin in cells for high-resolution imaging. Our findings highlight the need for further improvements in labeling methods to fully exploit the potential of molecular-scale optical three-dimensional resolution.
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA
(2022)
Article
Chemistry, Multidisciplinary
Miguel Lopez-Tena, Emma E. Watson, Patrick Romanens, Nicolas Winssinger
Summary: The exceptional hybridization properties of peptide nucleic acids (PNAs) coupled with the ease of their synthesis has made them a desirable platform for diagnostics, therapeutics and supramolecular engineering. The synthesis of a universal gamma-propargyl-PNA backbone from serine, and its acylation with the four DNA canonical nucleobases, is detailed in this paper. The availability of serine as d or l enantiomer provides simple access to PNA oligomers for hybridization with natural oligonucleotides or for orthogonal hybridization circuitry. Late-stage conjugation enables optimization of the physicochemical properties.
HELVETICA CHIMICA ACTA
(2023)
Article
Chemistry, Multidisciplinary
Javier Cabello-Garcia, Wooli Bae, Guy-Bart Stan, Thomas E. Ouldridge
Summary: The use of templates for sequence-controlled assemblies, particularly in long polymers, is a well-established method. However, the transient template recognition interactions during the biogenesis of sequence-controlled polymers can disrupt the equilibrium, leading to the production of far-from-equilibrium output. Handhold-mediated strand displacement (HMSD) is proposed as an alternative mechanism to generate out-of-equilibrium products by decoupling drive and specificity in DNA-based reactions.
Review
Chemistry, Inorganic & Nuclear
Min Yang, Longjiao Zhu, Wenping Yang, Wentao Xu
Summary: This article provides a comprehensive review of the recent advances in nucleic acid-mediated silver nanoclusters that first emerged in 2007. It focuses on the properties and structures of nucleic acid-templated silver nanoclusters, as well as the regulation of their properties by nucleic acid sequences, conformation, and structure. The most recent advances in nucleic acid-templated silver nanoclusters in biological detection are highlighted. Current challenges, prospects, and future directions are also discussed.
COORDINATION CHEMISTRY REVIEWS
(2023)
Article
Multidisciplinary Sciences
Qiaoqiao Ruan, Cheng Zhao
Summary: A protocol is provided for better control of protein labeling using Copper-free Click Chemistry reagents. This approach offers a simpler and more economical way to perform microscale labeling and has been shown to provide more stable conjugation than standard NHS-fluorophore labeling.
SCIENTIFIC REPORTS
(2023)
Article
Chemistry, Multidisciplinary
Xinlei Shi, Lin Zhu, Hui Yu, Ziqing Tang, Shaoping Lu, Haiyan Yin, Min You, Gengzhi Sun, Qiang Chen
Summary: Flexible strain sensors, especially those based on cracks, have attracted great attention due to their high sensitivity and potential applications in health monitoring and human-machine interactions. However, the weak bonding between the conductive layer and elastic substrate leads to poor durability. In this study, a strategy using interfacial click chemistry was proposed to enhance the adhesion strength and improve the durability of the strain sensors.
ADVANCED FUNCTIONAL MATERIALS
(2023)
Review
Biochemistry & Molecular Biology
Oleg L. Bodulev, Ivan Yu. Sakharov
Summary: The review explores modern methods for quantitative and semi-quantitative analysis of miRNAs, a type of small non-coding RNAs that play significant roles in various biological processes such as development, differentiation, metabolism, and immune response. miRNAs are considered as promising biomarkers in the diagnosis of different diseases.
BIOCHEMISTRY-MOSCOW
(2022)
Article
Chemistry, Multidisciplinary
Mathias B. Danielsen, Niels Johan Christensen, Per T. Jorgensen, Knud J. Jensen, Jesper Wengel, Chenguang Lou
Summary: Cationic moieties attached to oligonucleotides increased binding affinity and stability, with the 2'-amino-LNA analogue carrying a triaminated linker showing the most pronounced effect. Molecular modeling revealed salt-bridge formation between positively charged polyamine moieties and the dsDNA targets, resulting in the observed triplex stabilization. All investigated monomers showed increased resistance against 3'-nucleolytic digestion.
CHEMISTRY-A EUROPEAN JOURNAL
(2021)
Review
Biotechnology & Applied Microbiology
Maja van Hees, Sofie Slott, Anders Hojgaard Hansen, Heon Seok Kim, Hanlee P. Ji, Kira Astakhova
Summary: This article introduces new approaches for improving cellular uptake and endosomal escape of CRISPR-Cas9, with a focus on non-viral carriers. It also discusses the use of peptide and nanoparticle-based systems as platforms for in vivo CRISPR-Cas9 delivery.
Article
Biochemical Research Methods
Anders Dinesen, Alexander Winther, Archie Wall, Anders Maercher, Johan Palmfeldt, Vijay Chudasama, Jesper Wengel, Kurt Gothelf, James R. Baker, Kenneth A. Howard
Summary: This study aims to improve the stability of albumin-nucleic acid biomolecular drug designs by employing a fast hydrolyzing linker and nuclease resistant nucleotide analogues. The results show that the stabilized biomolecular constructs have high serum stability and retain module functionality, promoting the drug delivery potential of this biomolecular platform.
BIOCONJUGATE CHEMISTRY
(2022)
Article
Nanoscience & Nanotechnology
Daniela Araujo, Dalila Mil-Homens, Maria Elisa Rodrigues, Mariana Henriques, Per Trolle Jorgensen, Jesper Wengel, Sonia Silva
Summary: This study compared the efficacy of five different LNA-based antisense oligonucleotides (ASO) in controlling EFG1 gene expression and modulating filamentation and virulence of Candida albicans. The results showed that all LNA-ASOs significantly reduced filamentation and controlled EFG1 gene expression in vitro. In an in vivo model, important differences were observed in terms of reducing C. albicans virulence among the five LNA-ASOs.
NANOMEDICINE-NANOTECHNOLOGY BIOLOGY AND MEDICINE
(2022)
Article
Pharmacology & Pharmacy
Mateusz D. Tomczyk, Mariusz Zalewski, Per T. Jorgensen, Jesper Wengel, Krzysztof Walczak
Summary: The study presents novel macrocyclic polyamine-oligonucleotide conjugates and investigates their hybridization properties and thermal stability. By performing a Cu(I)-catalyzed azide-alkyne cycloaddition, macrocyclic polyamines and two DNA intercalating dyes are attached to oligonucleotides. The results show that the macrocyclic polyamine moiety has an additive and destabilizing effect on the duplex, while placing the hydrophobic dye opposite to the macrocyclic polyamine can increase the thermal stability of the duplex.
Article
Biochemistry & Molecular Biology
Jolanta Lisowiec-Wachnicka, Mathias B. Danielsen, Eugenie Abi Nader, Per T. Jorgensen, Jesper Wengel, Anna Pasternak
Summary: This study analyzed the impact of modified nucleotides on RNase H-mediated gene silencing. The results showed that introducing two LNA residues at specific positions is sufficient for efficient knock-down of the beta-actin gene. Moreover, the presence of other modified nucleotides and hairpins within the gapmers further enhanced the inhibition of beta-actin expression.
Letter
Oncology
Pilar Fajardo, Maria Taskova, Miguel A. Martin-Serrano, Jonas Hansen, Sofie Slott, Anna K. Jakobsen, Marie-Louise Wibom, Benat Salegi, Alberto Munoz, Antonio Barbachano, Arpita Sharma, John Mark Gubatan, Aida Habtezion, Juan J. Sanz-Ezquerro, Kira Astakhova, Ana Cuenda
CANCER COMMUNICATIONS
(2022)
Article
Microbiology
Andreia S. Azevedo, Ricardo M. Fernandes, Ana R. Faria, Oscar F. Silvestre, Jana B. Nieder, Chenguang Lou, Jesper Wengel, Carina Almeida, Nuno F. Azevedo
Summary: This study aimed to combine nucleic acid mimics (NAMs) and spectral image analysis to develop a new FISH variant, spectral imaging-NAM-FISH (SI-NAM-FISH), for multiplexed, robust, and rapid detection of clinical pathogens.
FRONTIERS IN MICROBIOLOGY
(2022)
Article
Medicine, Research & Experimental
Joerg Duschmale, Adrian Schaeublin, Erik Funder, Steffen Schmidt, Lukasz J. Kielpinski, Helle Nymark, Klaus Jensen, Troels Koch, Martina Duschmale, Erich Koller, Marianne Ravn Moller, Simone Schadt, Christophe Husser, Andreas Brink, Sabine Sewing, Tanja Minz, Jesper Wengel, Konrad Bleicher, Meiling Li
Summary: The introduction of sulfur into chemically synthesized oligonucleotides creates stereocenters on phosphorus atoms. Only recently has it become possible to synthesize fully stereodefined antisense oligonucleotides. This article describes the application of symmetrical non-bridging PS2 linkages in the context of stereodefined locked nucleic acids (LNAs) antisense oligonucleotides, aiming to reduce chiral complexity and ultimately result in single molecules.
MOLECULAR THERAPY-NUCLEIC ACIDS
(2022)
Article
Biochemistry & Molecular Biology
Osama Saher, Eman M. M. Zaghloul, Tea Umek, Daniel W. W. Hagey, Negin Mozafari, Mathias B. B. Danielsen, Alaa S. S. Gouda, Karin E. E. Lundin, Per T. T. Jorgensen, Jesper Wengel, C. I. Edvard Smith, Rula Zain
Summary: Huntington's disease is a neurodegenerative disorder caused by an abnormal increase in the length of a specific nucleotide repeat in the Huntingtin gene. A novel strategy using chemically modified oligonucleotides was found to effectively downregulate the mutant Huntingtin mRNA and protein, suggesting therapeutic potential. This study investigated the effects of different length, LNA content, and fatty acid modification of the antigene oligonucleotides on Huntingtin expression, and identified an optimized design for potential DNA-targeting therapeutics.
NUCLEIC ACID THERAPEUTICS
(2023)
Article
Chemistry, Multidisciplinary
Weiguang Jin, Xin Li, Gael Clergeaud, Roslyn M. Ray, Marie Karen Tracy Hong Lin, Thomas Lars Andresen, Charlotte Held Gotfredsen, Martin Nielsen, Kira Astakhova, Katrine Qvortrup
Summary: This study presents a novel strategy that utilizes metalloporphyrin cages to protect and prolong the half-lives of small RNAs (sRNAs). The cage binding also facilitates the internalization of sRNAs, and the released sRNAs maintain their genetic activity in an acidic intracellular environment. Moreover, the photodynamic properties of the cage enable efficient in vitro cell killing in breast cancer treatment.
CELL REPORTS PHYSICAL SCIENCE
(2022)
Article
Chemistry, Analytical
Adriain Hernaindez Bustos, Elisa Martiny, Nadia Bom Pedersen, Rohith Pavan Parvathaneni, Jonas Hansen, Hanlee P. P. Ji, Kira Astakhova
Summary: We present an amplification-free genotyping method for determining the number of human short tandem repeats (STRs). This method, which does not require polymerase amplification, allows for accurate detection of STRs in a short timeframe and with high target DNA enrichment. The results obtained using this method are comparable to those obtained from PCR-based assays.
ANALYTICAL CHEMISTRY
(2023)
Article
Biochemistry & Molecular Biology
Maria Izabel Muniz, Adrian H. Bustos, Sofie Slott, Kira Astakhova, Gerald Weber
Summary: Monovalent and divalent cations have important roles in living cells and molecular techniques like PCR. This study examines DNA melting temperatures in magnesium and magnesium-potassium buffers using a mesoscopic model. The results are compared to previous calculations for sodium ions in terms of equivalent sodium concentration and ionic strength. The study finds that Morse potentials for hydrogen bonding are constant regardless of cation conditions, but stacking interactions are influenced by ionic strength and cation valence. The strongest variations in ionic strength occur at the sequence terminals, indicating a strong dependence of end-to-end interactions on cation valence and ionic strength.
BIOPHYSICAL CHEMISTRY
(2023)
Article
Chemistry, Organic
Sofie Slott, Kira Astakhova
Summary: In this study, a new approach was described for the synthesis of microRNA pools targeting breast cancer cells. The microRNAs were synthesized simultaneously on the same solid support using the Tandem Oligonucleotide Synthesis strategy. The developed phosphoramidites allowed efficient cleavage of the microRNAs and were used to make linear and branched pools to improve product yields. This approach provides a high-yield method for synthesizing microRNA pools, which is important for nucleic acid research and technology.
JOURNAL OF ORGANIC CHEMISTRY
(2023)
Article
Multidisciplinary Sciences
Sofie Slott, Cecilie Schioth Kruger-Jensen, Izabela Ferreira da Silva, Nadia Bom Pedersen, Kira Astakhova
Summary: We present a quantitative detection method for mutated microRNA in human plasma samples. Using specific oligonucleotides designed from a Peyrard-Bishop model, we accurately predict the recognition affinity and specificity of the target and probe. Our amplification-free tandem bead-based hybridization assay achieves a limit of detection of 2.2 pM, allowing identification of single-nucleotide polymorphism mismatch profiles in microRNA-128-2-3p that correlate positively with inflammatory colitis and colorectal cancer.